We hope to elucidate new features of the eukaryotic transcription apparatus involved in the regulation of gene expression as exemplified by studies on Drosophila melanogaster. Our approach is to isolate, characterize and experimentally exploit mutants specifically altered in RNA polymerase II, the enzyme that transcribes structural gene information. We previously isolated an amanitin-resistant mutant RpIIC4, or simply C4) with an altered, amanitin-resistant RNA polymerase II and more recently we isolated a number of additional alleles of the C4 locus. This locus apparently is the structural gene for the subunit of Drosophila RNA polymerase II that comprises the amanitin-binding site. We now hope to isolate additional mutants in loci coding for several of the multiple subunits of RNA polymerase II, to map each locus, to characterize the altered enzymes, to identify the subunit encoded by each locus, and to use the mutants to elucidate the roles of the subunits in catalysis or regulation of RNA synthesis. We also hope to learn much about the enzymology and protein chemistry of RNA polymerase II per se during the course of these studies.